Dispatches from the cutting edge of flagellar biology, part 2

Following on from my previous post, the second set of take-away messages from Keiichi Namba's presentation last week all centre on the ATPase associated with the flagellar protein export system. But first some background...

Since the early 1990s, it has been known, from sequence comparisons, that the flagellar ATPase (FliI) is homologous to the alpha and beta subunits of the F-type ATPase, a transmembrane protein complex (see figure) found in bacteria, mitochondria and chloroplasts (see http://www.atpsynthase.info). 

In 2003, Nick Matzke (then at the NCSE and so a couple of years later science adviser to the plaintiffs in the Dover trial) wrote an essay summarising plausible evolutionary scenarios for the origin of the bacterial flagellum. He noted a couple of previous suggestions that the proto-flagellum might have originated from the F-type ATPase. Crucially, he predicted that additional homologies would be found between components of the F-type ATPase and the flagellar protein export apparatus, for example between the b subunit of the ATPase and FliH and between the delta subunit and FliJ. 

In 2006, I confirmed one of Nick's hunches through homology searches, showing that part of FliH was homologous to the b subunit. However, things turned out slightly different from Nick's predictions in that FliH is actual of a fusion of domains homologous to the b subunit and the delta subunit.

Last year Namba's group published the structure of FliI and confirmed the striking homology with the F-type ATPase enzymatic subunits. At that stage in the game, it had become clear that the ATPase was a universal component not just of flagellar export systems but also of non-flagellar type III secretion systems. Also, if it was also clear that if one knocked out the gene for FliI, one abolished flagellar biosynthesis. Thus, just about everyone in the field accepted that FliI was an essential component of the flagellar apparatus and that it energised secretion of proteins through the protein export system. In other words, if there were anything to the idea, put forward by Behe and others in the ID movement, that the flagellum showed "irreducible complexity", even experts might have accepted that FliI was one of the "irreducible" components!!

BUT earlier this year, Minamino and Namba (and independently a team headed by Kelly Hughes in the US) overturned all our assumptions by showing that it was perfectly possible to make flagella without FliI--what you needed to do was knock out FliH at the same time. Somehow or other FliH, which usually interacts with FliI, gums up the export apparatus in the absence of FliI. So, bang goes another pillar of support for the ID argument! In fact, it appears that flagellar protein export is powered not primarily by the ATPase by the proton-motive force. 

Anyhow, to get back to what Namba said at the Bristol meeting last week....

He provided a run through of all the work leading up to his recent Nature article on the dispensibility of FliI. I was then very proud to see him cite my paper on the FliH/F-type ATPase homology. But then he provided the final piece in the jigsaw (and Nick Matzke's ears should prick up at this point)!

Namba and colleagues have now solved the structure of FliJ, another protein that interacts with FliI and FliH. And what they found was clear evidence of homology with yet another protein from the F-type ATPase--the gamma subunit!

So, now we have deep and broad homologies between the flagellum and the F-type ATPase, just as Nick predicted. This provides another nail in the coffin of the idea that flagellum was intelligently designed. If the flagellum were the product of intelligent design, particularly by an omniscient deity, the designer could have custom-built it from scratch, so it need not resemble anything else in nature. By contrast, the processes of evolution tends to cobble together and tweak already existing components (something Francois Jacob called bricolage)--and slowly but steadily it is become clear that the flagellum has been built this way. 

There are now likely to be serious scientific payoffs--what all these homologies mean is going to occupy Namba et al for years to come, and it's a fair bet that comparisons between the two protein complexes are likely to clarify the structures and functions of both systems. 

Science rolls on while ID stays stuck in its non-productive rut! What we need more of is science!